Minireviews
Iron Homeostasis: Recently Identified Proteins Provide Insight into Novel Control Mechanisms*

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Iron is an essential nutrient required for a variety of biochemical processes. It is a vital component of the heme in hemoglobin, myoglobin, and cytochromes and is also an essential cofactor for non-heme enzymes such as ribonucleotide reductase, the limiting enzyme for DNA synthesis. When in excess, iron is toxic because it generates superoxide anions and hydroxyl radicals that react readily with biological molecules, including proteins, lipids, and DNA. As a result, humans possess elegant control mechanisms to maintain iron homeostasis by coordinately regulating iron absorption, iron recycling, and mobilization of stored iron. Disruption of these processes causes either iron-deficient anemia or iron overload disorders. In this minireview, we focus on the roles of recently identified proteins in the regulation of iron homeostasis.

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This work was supported, in whole or in part, by National Institutes of Health Grants DK054488 and DK072166 (to C. A. E.) and DK080765 (to A.-S. Z.). The work was also supported by Amgen (to A.-S. Z.). This is the first article of three in the Thematic Minireview Series on Metals in Biology. This minireview will be reprinted in the 2009 Minireview Compendium, which will be available in January, 2010.